To study copper metabolism in vivo the fate of Cu67 is followed after its intravenous injection or the fate of both Cu67 and Cu64 are followed after giving one of the isotopes intravenously and the other by mouth. Subsequently, measurements are made of radioactivity in the whole body, liver, red cells, ceruloplasmin, ceruloplasmin-free plasma, urine and feces. The data obtained are being analyzed by computer using curve-fitting techniques and a multicompartmental model of copper metabolism. The computer analysis enables various parameters of copper metabolism to be quantitated, in particular the kinetics of intestinal absorption, hepatic uptake, biliary excretion and incorporation into ceruloplasmin. The primary goal of these studies is to obtain an improved understanding of copper metabolism in normal subjects and in patients with diseases associated with increased deposition of copper in the liver, notably Wilson's disease and primary biliary cirrhosis. Another goal is to determine whether a set of abnormalities of radiocopper kinetics can be defined which would enable subjects who are heterozygous for Wilson's disease to be distinguished from those who are homozygous and those who are neither homozygous nor heterozygous for this disease.